Invasive Fungal Infections in Adults with Newly Diagnosed AML Undergoing Intensive Chemotherapy: Characterization, Risk Factors, and Outcomes in a Single Institution

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 4254-4254
Author(s):  
Kit Lu ◽  
Dionissios Neofytos ◽  
Amanda Blackford ◽  
Amy Seung ◽  
Judith E. Karp
Keyword(s):  
Risk Factors ◽  
Overall Survival ◽  
Bacterial Infections ◽  
Conflicts Of Interest ◽  
Fungal Infections ◽  
Significant Risk ◽  
Invasive Fungal Infections ◽  
Myelogenous Leukemia ◽  
Newly Diagnosed ◽  
European Organization

Abstract Abstract 4254 Background: Invasive fungal infections (IFI) are a significant cause of morbidity and mortality in patients with acute myelogenous leukemia (AML) undergoing chemotherapy treatment. However, the epidemiology, risk factors, and outcomes of IFI in these patients have been poorly described. Methods: A single-center retrospective analysis was performed to study the epidemiology, risk factors, clinical outcomes, and mortality predictors of IFIs in AML patients undergoing intensive, multi-agent induction timed sequential therapy (TST) between January 2005 and June 2010. Newly diagnosed AML patients, with exception of acute promyelocytic leukemia, were studied. IFIs were defined using the European Organization for Research and Treatment of Cancer/Mycoses Study Group (EORTC/MSG) criteria. Results: 254 consecutive patients (57% male; median age 54, range 20–78) were analyzed. 123 (48%) of patients had an IFI; of which, 15 patients (12%) had a proven candidal infection, and 108 patients (88%) had a mould infection (5 proven/probable (5%) and 103 (95%) possible mould infections). 237 (93%) patients received antifungal therapy during their treatment course (median day 8, range day -15 to 30). Of those, 63 (27%) received monotherapy (46% liposomal amphotericin, 44% voriconazole) and the rest received multiple antifungal agents. Significant risk factors and trends for developing +IFI shown from univariate analyses are listed in Table 1. Prolonged neutropenia, duration of mucositis, and concurrent bacterial infections did not significantly affect the development of +IFI. Using multivariate analyses, mortality was impacted by patients’ baseline organ function (p=0.002 [1.3,3.1]), specifically, by bilirubin < 2 mg/dL (p=0.003 [1.38,4.57]) and creatinine < 1.5 mg/dL (p=0.01 [1.23,5.4]). Patients with +IFI did not significantly impact overall survival. However, patients with candidal IFIs had a significantly lower overall survival compared to patients with mould IFIs and no IFI (HR 2.01 [1.06, 3.8]) (Figure 1). Candida colonization prior to or during the first week of chemotherapy, and development of mucositis were associated with the development of candidal IFIs (p=0.07). Conclusion: IFIs, particularly mould infections, remain a significant problem in patients with AML. Although overall survival did not appear to be significantly affected by mould infections, patients with candidal infections were more likely to die. Identification of risk factors for each type of IFIs may help to develop effective targeted preventive antifungal strategies. Disclosures: No relevant conflicts of interest to declare.

Response and Overall Survival Is Impaired in Obese Patients with Acute Myelogenous Leukemia

Blood ◽  
2012 ◽  
Vol 120 (21) ◽  
pp. 1522-1522
Author(s):  
Martina Crysandt ◽  
Edgar Jost ◽  
Susanne Isfort ◽  
Tim H Brümmendorf ◽  
Stefan Wilop
Keyword(s):  
Risk Factors ◽  
Overall Survival ◽  
Induction Therapy ◽  
Risk Group ◽  
Myelogenous Leukemia ◽  
Prognostic Impact ◽  
Obese Patients ◽  
Newly Diagnosed ◽  
Laboratory Parameters

Abstract Abstract 1522 Introduction Dose calculation of chemotherapeutic agents is mainly based on body surface area (BSA). Historically, in many institutions, doses are not adapted to a BSA above 2 sqm, although recent data suggested that this relative dose reduction in patients above 2 sqm is associated with a worse outcome. Obesity is a widespread and increasing phenomenon in the developed countries and is mainly defined by the body mass index (BMI). It is known, that the risk to develop haematological or solid malignancies is increased in obese patients – and, additionally, weight influences outcome in several tumours. Therefore, in our study, we analyzed the prognostic impact of obesity in newly diagnosed AML regarding the response to the first cycle of induction therapy and overall survival. Methods We identified 145 patients with newly diagnosed AML who were treated with induction therapy containing cytarabine and an anthracycline in our institution. Clinical data including several laboratory parameters associated with nutritional status (cholesterol, triglycerides, protein, C-reactive protein, albumin, lymphocyte count, transferrin, pseudo-cholinesterase, fT3, b-type natriuretic peptide), long-term medication with statins, chemotherapy dosing as well as response and overall survival have been assessed retrospectively from the institution's database. In our institution, all patients with a high BSA received a chemotherapy-dose calculated with a cut-off of not more than 2 sqm. Results In our cohort, median BMI was 25.2 kg/sqm (range 17.0 – 48.1). Seventeen patients had a BMI above 31 kg/sqm, 128 below. The median BSA of all patients was 1.83 sqm (range 1.49 – 2.40). In 41 patients, chemotherapy doses have been adjusted owing to a BSA of more than 2 sqm. We included cytogenetic risk group, BMI, BSA above 2.0 sqm, weight, long-term medication with statins and laboratory parameters in our univariate and multivariate analysis. Only cytogenetic risk group (p=0.001), triglycerides (p=0.008) and the BMI (p=0.032) were independent risk factors for overall survival. Univariate analysis showed similar results. Patients with a BMI >31 showed a significantly worse response (PR + CR) on first induction therapy (47.1% vs. 74.8%, p=0.018) and a shorter median survival (11.2 vs. 25.1 months, p=0.004). Both BMI-groups showed the same distribution of well-known risk factors including age, cytogenetic risk groups and secondary AML. Discussion/Conclusion In our cohort, a high BMI was associated with poorer response and impaired overall survival, whereas BSA was not. This leads to the conclusion, that the adverse effect may be mediated by obesity itself and not caused by underdosing of chemotherapy. Although an effect of BMI is known from several solid tumours, the reason remains unclear. Possible explanations include altered metabolisation and production of growth factors in adipose tissue (possibly indicated by elevated triglycerides), impaired or accelerated hepatic drug activation and/or metabolisation or impact on immune function. This study is limited by the retrospective single-center design and the relatively small patient number. Nevertheless, the data clearly confirmed other well established risk factors like the cytogenetic risk group supporting the validity of this approach. The study results suggest BMI as an independent risk factor for AML. Disclosures: No relevant conflicts of interest to declare.

Exchange Transfusion and Leukapheresis in Pediatric AML Patients with High Risk of Early Death for Bleeding and Leukostasis

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 3741-3741
Author(s):  
Ursula Creutzig ◽  
Claudia Rossig ◽  
Michael Dworzak ◽  
Arendt von Stackelberg ◽  
Wilhelm Woessmann ◽  
...  
Keyword(s):  
Risk Factors ◽  
High Risk ◽  
Exchange Transfusion ◽  
Clinical Symptoms ◽  
Conflicts Of Interest ◽  
Significant Risk ◽  
Early Death ◽  
Myelogenous Leukemia ◽  
Acute Monocytic Leukemia ◽  
Metabolic Disturbances

Abstract Background. The risk of early death (ED) due to bleeding and/or leukostasis is high in AML patients with initial hyperleukocytosis (white blood cell count [WBC] > 100 000/µl) and highest in those with hyperleukocytosis and mono- or myelomonocytic leukemia (FAB M4/M5). (Creutzig, et al 1987) Within the AML-BFM studies, emergency strategies for children with AML and high risk for bleeding and leukostasis included exchange transfusion (ET) or leukapheresis (LPh). In order to determine whether these interventions reduced the rate of ED, 1251 AML-BFM patients from the trials AML-BFM 98 and 04 were analyzed. Risk factors for ED and interventions performed were verified focusing on patients with hyperleukocytosis. Patients . 238 of 1251 (19%) AML-patients <18 years of age (FAB M3 excluded) presented with hyperleukocytosis. Twenty-three out of 1251 (1.8%) patients died by bleeding and leukostasis within 15 days from diagnosis, 18 (78%) of these 23 ED patients had hyperleukocytosis. Seventy-two patients received ET and 17 LPh (including 14 patients with WBC counts < 100 000/µl). 149 patients with hyperleukocytosis did not receive ET/LPh. The median age of patients receiving ET was significantly lower compared to those with LPh (3.5 years vs 12.6 years, p = 0.015). WBC counts were similar in both treatment groups (ET median 224 000/µl vs LPh 218 000/µl, p = 0.20). Results. The percentage of ED by bleeding/leukostasis increased with higher WBC counts and was highest in 105 patients with WBC > 200 000/µl (14.3%). The ED rates were even higher in patients with FAB M4/M5 and hyperleukocytosis >200 000/µl compared to others with WBC >200 000/µl (M4/M5 13/65 [20%] vs. others 2/40 [5%], p=0.04). Patients with WBC counts >200 000/µl did slightly better with ET or LPh compared to those without ET/LPh (ED rate 7.5 % vs 21.2 %, p=0.055). Patients with WBC between 100 000/µl and 200 000/µl received ET/LPh less frequently compared to those with WBC >200 000/µl (22/133 [17%] vs. 53/105 [50%]). ET/LPh was mainly given in case of clinical symptoms of bleeding or leukostasis or coagulopathies or insufficient reduction (or increase) of WBC counts despite low dose chemotherapy. 15/80 (19%) patients with FAB M4/5 and WBC 100 000-200 000/µl received ET/LPh and none of these patients died early. ET/LPh was even given in 14 patients with WBC <100 000/µl because of clinical symptoms of bleeding or leukostasis or coagulopathies or rising WBC counts. In multivariate analysis WBC >200 000/µl was the strongest independent risk factor for ED (hazard ratio =15.0, 95% confidence interval 4.9-46.3, p(chi)<0.0001). FAB M4/M5 subtypes, general condition grade 4 and initial bleeding were also significant risk factors. Application of ET/LPh seems to have a non-significant benefit for a reduced ED rate by bleeding/leukostasis (p=0.13). The assessment of the general clinical condition of the patients plays a major role for the decision for ET/LPh. However, this possibly selective cofactor could not be included completely in our calculation because of lack of standardized assessments and documentation of clinical reasons for decision making in particular in patients without ET/LPh. There was no difference in ED rates between ET and LPh. (2/17 vs 5/72, p =0.61). Compared to LPh, ET can be given without time delay. ET is easier to perform especially in young children who need smaller exchange volumes, as well as in adolescents where it can be applied also as partial ET. ET also corrects metabolic disturbances and avoids deterioration of coagulation. Conclusion. Our data confirm the high risk of bleeding/leukostasis in patients with hyperleukocytosis. Although we could only disclose a trend for a clinical benefit of ET/LPh in this retrospective analysis - probably due to some negative selection bias in patients with the intervention - we strongly advocate ET/LPh in AML patients with WBC >200 000/µl, and in particular in those with FAB M4/M5 subtypes or with clinical symptoms of bleeding or leukostasis or coagulopathies even with lower WBC (100 000/µl - 200 000/µl). Creutzig, U. et al. (1987) Early deaths due to hemorrhage and leukostasis in childhood acute myelogenous leukemia: Associations with hyperleukocytosis and acute monocytic leukemia. Cancer,60, 3071-3079. Disclosures No relevant conflicts of interest to declare.

scholarly journals Ruxolitinib Combined with Dexamethasone in Adult Patients with Secondary HLH：a Single-Centre Pilot Trial

Blood ◽  
2021 ◽  
Vol 138 (Supplement 1) ◽  
pp. 198-198
Author(s):  
De Zhou ◽  
Xianbo Huang ◽  
Mixue Xie ◽  
Hong-Hu Zhu ◽  
Jie Jin ◽  
...  
Keyword(s):  
Overall Survival ◽  
Bacterial Infections ◽  
Conflicts Of Interest ◽  
Pilot Trial ◽  
Adult Patients ◽  
Unknown Etiology ◽  
Massive Hemoptysis ◽  
Rapid Progression ◽  
Newly Diagnosed

Abstract Background Hemophagocytic lymphohistiocytosis (HLH) is a cytokine-driven inflammatory syndrome associated with hereditary or acquired immune-dysregulation. The frontline therapy for secondary HLH in adult patients is HLH-1994 regimen, however overall survival of these patients remains suboptimal. Janus family kinases JAK1 and JAK2 are hallmarks of the final common pathway in HLH, and ruxolitinib (an oral JAK inhibitor) has shown favorable efficacy and safety in murine models and clinical trials. Recently, Lauren K. Meyer et al demonstrate that hypercytokinemia of HLH reduces the apoptotic potential of CD8 T cells leading to relative dexamethasone resistance, and this apoptotic potential is restored both in vitro and vivo when exposure to ruxolitinib. This finding provide rationale for combining dexamethasone and ruxolitinib to enhance the lymphotoxic effects of dexamethasone and thus improve the outcomes for patients with HLH. We were very interested in this finding and conducted this pilot trial in adult patients with secondary HLH. Methods We managed 8 newly diagnosed HLH patients with ruxolitinib combined with dexamethasone or methylprednisolone from April 1, 2021 to May 31, 2021 in the First Affiliated Hospital of Medical School of Zhejiang University. All patients fulfilled at least five of the eight HLH-2004 diagnostic criteria and the etiology was not identified at the time. The regimen in detail was ruxolitinib 15mg po. bid d1-56, dexamethasone 10mg/m 2 d1-14, 5mg/ m 2 d15-28, 2.5 mg/m 2 d29-42, 1.25mg/m 2 d43-49, reduce the dosage until withdrawal d50-56 (For patients with liver insufficiency, dexamethasone is replaced with the same equivalent of methylprednisolone). Once the patient's primary cause had been identified, we wound begin primary disease treatment immediately. Results Eight newly diagnosed HLH patients without previous treatment were enrolled in this study with a median follow-up of 102 (2-122) days, including 5 cases of lymphoma-associated HLH, one case of bacterial infections-associated HLH, and 2 cases of unknown etiology. The overall response rate at the end of HLH treatment was 87.5% (7/8), with 50% (4/8) in complete response (CR), 37.5% (3/8) in partial response (PR), and 12.5% (1/8) in no response. Among the patients achieving CR, 100% (4/4) maintained CR condition for＞2 months. 2-month overall survival was 75% (6/8), one patient was dead because of lymphoma associated HLH progression, another patient was dead because of bronchiectasis with massive hemoptysis after the HLH was under control. For the lymphoma-associated HLH subgroup, 4 of 5 patients responded to ruxolitinib combined with dexamethasone, three patients successfully bridged to chemotherapy after diagnosis of lymphoma; One patient defused to chemotherapy because she was 77 years old and had severe bronchiectasis; the patient with NR was dead in 2 days due to the rapid progression of disease. No treatment-related deaths were observed. Conclusions In our trial, ruxolitinib combined with dexamethasone regimen initially demonstrated favorable efficacy in newly diagnosed adult patients with secondary HLH. Especially for patients with lymphoma-associated hemophagocytic syndrome, it is an efficient and safe bridging therapy while waiting for pathological diagnosis. This novel treaiment is promising, and should be evaluated in larger sample size studies. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Epidemiology and Risk Factors of Invasive Fungal Infections Among 795 Patients with Chronic Lymphocytic Leukemia from the Padua University

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2527-2527 ◽  
Author(s):  
Andrea Visentin ◽  
Carmela Gurrieri ◽  
Silvia Imbergamo ◽  
Federica Lessi ◽  
Speranza Antonia Di Maggio ◽  
...  
Keyword(s):  
Overall Survival ◽  
Chronic Lymphocytic Leukemia ◽  
Bacterial Infections ◽  
Fungal Infections ◽  
Invasive Fungal Infections ◽  
Lymphocytic Leukemia ◽  
Hematopoietic Stem ◽  
Anova Test ◽  
Risk Of Death

Abstract Background Invasive fungal infections (IFI) are serious and life-threatening complications of hematological malignancies particularly in patients affected by acute myeloid leukemia and following hematopoietic stem cell transplantation. However, only few epidemiological data concerning fungal infections in chroniclymphoproliferativedisorders are available. In this work we aimed to identify the clinical and biological features of patients with chronic lymphocytic leukemia (CLL) affected by IFI. Methods We performed a single-center retrospective study based on the CLL patients referred to the Hematology Unit of University of Padua from 1983 to 2015. IFI were defined as infective events caused by yeasts ormouldsthat required inpatient management and/or intravenous antifungal therapies. We included only proven and probable IFI. Time to IFI (TIFI) and overall survival (OS) were calculated from the date of CLL diagnosis to IFI development or death (event), respectively, or last available follow-up (censored). Diagnostic work-up of fungal infection included blood cultures, serumgalactomannanantigen test for 3 consecutive days (cut-off 0.5), β-1,3-(D)-glucanand high resolution chest computed tomography andbronchoalveolarlavages when clinically indicated. We also collected the closest immunoglobulin (IG) levels data before the onset of each IFI or serious bacterial infective events. IGs measured during infections were not included in the analysis, because they could have been influenced by the infectious event. The last available serum IG levels were considered for patients who did not suffer from any IFI. Results 795 patients with CLL were recruited in this study. 60% were male and the median age at diagnosis and at IFI onset were 65 and 68 years, respectively. The median follow-up was 8.5 years and 316 patients required treatment during the follow-up. 11 out of 795 (1.4%) patients developed IFI during the follow-up. Among them, 7 patients (64%) had probable Aspergillosisand 4 had proven IFI (3 Aspergillusspp and 1 Candida kruseii) based on histological confirmation and/or microbiological isolation of the specific fungal agent. 9 patients wereBinet stage A, 2Binet B and noneBinet C at CLL diagnosis. The median lines of treatment were 5 ranging from 2 to 9. Six out of 11 (55%) patients showed high-risk cytogenetic by FISH analysis (11q or 17p deletion), 2 harbored complex karyotypes, 62% (5/8) hadunmutated IGVH gene. By Kaplan-Meyer analysis we showed that IFI occurred in 2.1% and 7.0% of the cohort after 10 and 20 years of follow-up, respectively (Figure 1A). However, considering the number of chemotherapy regimens, the estimated cumulative incidence of IFI was higher in patients who were treated with at least 4 lines of chemo-immunotherapy (10-year TIFI were 9.0% and 0.3%, p<0.0001, Figure 1B). IFI occurrence was associated with a very poor prognosis. In fact, the median overall survival of patients who developed IFI was 125 months as compared to 250 months of the remaining cohort (Log-rank test, p=0.0001, Figure 1C). Since IFI was itself the main cause of death of these subjects. In multivariable analysis, patients with IFI had almost 10 times higher-risk of death (HR 10, p=0.0012) that other patients. We demonstrated that, at the time of IFI events, patients had lower levels of IG as compared to a group of 72 patients who had serious bacterial infections or to 712 subjects who did not have any infections. The medianIgGlevels were 4.11, 6.38 and 8.38 g/L for patients with IFI, bacterial infections and without history of infections, respectively (ANOVA test, p<0.0001, Figure 1D). The median IgA levels were 0.35, 0.78 and 1.39 g/L for patients with IFI, bacterial and none infections, respectively (ANOVA test, p<0.0001, Figure 1E). The medianIgMlevels were 0.28, 0.59 and 0.65 g/L for patients with IFI, bacterial and none infections, respectively (ANOVA test, p=0.0038, Figure 1F). Conclusions Herein, we described the epidemiology of invasive fungal infections among a large cohort of CLL patients from a single institution over 32 years. We demonstrated that IFI significantly impacts on the survival of CLL patients and we provided evidence of the importance of previous chemo-immunotherapy and IG levels on the risk of developing IFI. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Risk of Early Mortality in Patients with Newly Diagnosed Multiple Myeloma

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 5306-5306
Author(s):  
Chia-Jen Liu ◽  
Pei Hsu ◽  
Ting-Wei Lin ◽  
Jyh-Pyng Gau ◽  
Liang-Tsai Hsiao ◽  
...  
Keyword(s):  
Risk Factors ◽  
Multiple Myeloma ◽  
Serum Albumin ◽  
Serum Calcium ◽  
Conflicts Of Interest ◽  
Significant Risk ◽  
High Serum ◽  
Early Mortality ◽  
Newly Diagnosed ◽  
Low Serum

Abstract Background The overall survival of patients with multiple myeloma has been improved greatly over the last two decades with the advances of treatment. Several studies reported that this improvement in survival has been ascribed to the broader use of novel drugs and autologous tandem transplantation. However, there were still a certain portion of myeloma patients died early after diagnosis. We therefore aim to investigate the risk factors of early mortality (death within 60 days after diagnosis) in patients with multiple myeloma. Patients and Methods We included in this study 451 consecutive patients with multiple myeloma, newly diagnosed at an Asian tertiary medical center between January 1, 2002 and April 30, 2015. A total 57 subjects who developed early mortality were identified. Risk factors for early mortality in myeloma patients were collected and analyzed. Results Compared with non-early mortality myeloma patients, early mortality patients had higher probability of being male, primary plasma cell leukemia, low platelet count, low serum albumin, high corrected serum calcium, high serum creatinine, high LDH, high serum β2-microglobulin, poor performance status, and high ISS stage. With multivariate analysis, we found that male (adjusted OR 2.93, 95% CI 1.17-7.31), serum albumin < 3.5g/dl (adjusted OR 2.76, 95% CI 1.17-6.52), corrected serum calcium ≥ 12mg/dl (adjusted OR 3.56, 95% CI 1.47-8.63) and LDH ≥ 250U/L (adjusted OR 3.30, 95% CI 1.62-6.74) were significant risk factors of early mortality. Pneumonia represented as the leading cause of early mortality in myeloma patients (n = 18, 31.5%), followed by renal failure (n = 7, 12.2%). Conclusion Early mortality rate is high (12.6%) in patients with multiple myeloma. Patients of male gender, low serum albumin, high corrected serum calcium and LDH are at risk of early mortality. More than one third myeloma patients (21 out of 57) who developed early mortality are died of infection. Identifying the risk group and providing prompt intervention, such as prophylaxis antibiotics, may reduce the incidence rate of early mortality and improve the life expectancy of myeloma patients. Disclosures No relevant conflicts of interest to declare.

scholarly journals The Significance of Inflammatory Markers in the Prognosis of Newly Diagnosed Multiple Myeloma Patients

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 15-15
Author(s):  
Lin Gui ◽  
Fei Wang ◽  
Jinning Shi ◽  
Baoan Chen
Keyword(s):  
Risk Factors ◽  
Multiple Myeloma ◽  
Overall Survival ◽  
Multivariate Analysis ◽  
Survival Time ◽  
Cox Regression ◽  
Conflicts Of Interest ◽  
Univariate Analysis ◽  
Rank Test ◽  
Newly Diagnosed

Objective: To explore the significance of the ratio of neutrophils to lymphocytes (NLR), monocytes to lymphocytes (MLR), and platelets to lymphocytes (PLR) in the prognosis of patients with newly diagnosed multiple myeloma. Methods: We retrospectively reviewed the data for 60 multiple myeloma patients who were diagnosed in Jiangning Hospital Affiliated to Nanjing Medical University from August 2011 to March 2020. According to NLR、MLR、PLR, the patients were divided into the low NLR group (NLR&lt;3.61) or high NLR group (NLR≥3.61), low MLR group (MLR&lt;0.33) or high MLR group (MLR ≥0.33), low PLR group (PLR&lt; 129.78) and high PLR group (PLR ≥129.78). Overall survival time (OS) was used as the prognostic evaluation criteria, and Kaplan-Meier survival curve, Log-rank test and Cox regression model were used to carry out univariate and multivariate analysis on clinical and laboratory parameters. Results: Among the 60 patients, 33 were male and 27 were female, the median age of onset was 65 years old, 19 were in the high NLR group, 41 were in the low NLR group, 24 were in the high MLR group, 36 were in the low MLR group, 26 were in the high PLR group, and 34 were in the low PLR group. The univariate analysis showed the prognosis was influenced by factors including NLR, PLR, age, ISS stages, hemoglobin (HGB), albumin (ALT). MLR, type of immunoglobulin, white globulin ratio (A/G), gender, β2-microglobulin, lactate dehydrogenase (LDH) and creatinine were not correlated with the total survival time of patients. The multivariate analysis showed that ISS III stages, PLR≥129.78、HGB&lt;100g/L were independent risk factors influencing the prognosis of MM patients. Conclusion: ISS III stages, PLR≥129.78、HGB&lt;100g/L are independent prognostic risk factors in newly diagnosed multiple myeloma patients, which can be used as an economical and effective method for early evaluation of patient prognosis. Key Wordsmultiple myeloma; overall survival; NLR; PLR; MLR Disclosures No relevant conflicts of interest to declare.

scholarly journals Clinical Outcomes of the Oral Suspension vs Delayed-Release Tablet Formulations of Posaconazole for Prophylaxis of Invasive Fungal Infections

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S86-S86
Author(s):  
Gregory B Tallman ◽  
Jon P Furuno ◽  
Brie N Noble ◽  
Joseph S Bubalo ◽  
Graeme N Forrest ◽  
...  
Keyword(s):  
Fungal Infections ◽  
Invasive Fungal Infections ◽  
Myelogenous Leukemia ◽  
University Hospital ◽  
Oral Suspension ◽  
Early Discontinuation ◽  
European Organization ◽  
Delayed Release ◽  
Research Grant ◽  
Release Tablet

Abstract Background Posaconazole is effective prophylaxis for invasive fungal infections (IFIs). We compared incidence of breakthrough IFI (bIFI) and early posaconazole discontinuation between patients receiving delayed-release tablet and oral suspension formulations. Methods This was a retrospective cohort study of patients receiving posaconazole at Oregon Health & Science University Hospital between 1/1/2010 and 6/30/2016. Oral suspension was the preferred formulation until 2/2014; afterwards the tablet was preferred. We included all courses of primary prophylaxis for each patient during the study period. Data were extracted from an electronic health record repository and via chart review. Three independent reviewers identified bIFI using European Organization for Research and Treatment of Cancer criteria. We assessed rationale for early discontinuation of posaconazole for patients that were still indicated for antifungal prophylaxis based on National Comprehensive Cancer Network (NCCN) criteria. Results 547 patients received 859 courses of posaconazole (53% oral suspension and 48% tablet). Prophylaxis was indicated according to NCCN criteria in 91% of courses. The primary indications for prophylaxis were acute myelogenous leukemia (68%), graft-vs-host disease (18%), and myelodysplastic syndrome (3%). There were no significant differences in demographics or indication between patients receiving the different formulations. The overall incidence rate of bIFI was 4.15/10,000 posaconazole-days (16 total bIFI events). Incidence of bIFI was not significantly different between patients receiving the different formulations (P = 0.92). Posaconazole was discontinued early in 147 (17%) courses; frequency of discontinuation was not significantly different between the tablet (20%) and oral suspension (15%) formulations (P = 0.10). The primary reasons for early discontinuation were elevated liver function tests or QT prolongation (25%), inability to take an oral formulation (17%), and drug cost (17%). Conclusion Among patients receiving posaconazole prophylaxis, incidence of bIFI was low and not significantly different between those receiving the tablet vs oral suspension formulations. Disclosures J. P. Furuno, Merck & Co.: Consultant and Grant Investigator, Consulting fee, Research grant and Speaker honorarium. J. S. Lewis II, Merck & Co.: Consultant, Consulting fee. J. C. McGregor, Merck & Co.: Grant Investigator, Research grant

scholarly journals 1095. Investigation of Risk Factors Associated with Serious Bacterial, Viral and Invasive Fungal Infections in Hematologic Patients on Ibrutinib

2020 ◽  
Vol 7 (Supplement_1) ◽  
pp. S576-S577
Author(s):  
Thomas Holowka ◽  
Harry Cheung ◽  
Maricar F Malinis ◽  
Sarah Perreault ◽  
Iris Isufi ◽  
...  
Keyword(s):  
Risk Factors ◽  
Fungal Infections ◽  
Antimicrobial Prophylaxis ◽  
Hematologic Malignancy ◽  
Invasive Fungal Infections ◽  
Risk Of Infection ◽  
Factors Associated ◽  
Serious Infection ◽  
Increased Risk ◽  
Serious Infections

Abstract Background Ibrutinib is a tyrosine kinase inhibitor used to treat hematologic malignancies that may increase the risk of serious infection including invasive fungal infections (IFI). In a study of 378 patients with hematologic malignancy on ibrutinib, serious infection and IFI occurred in 11% and 4% respectively (Varughese et al. Clin Infect Dis). The primary aims of our study were to determine the incidence of serious infection and associated risk factors in patients on ibrutinib. Methods We performed a retrospective analysis of patients with hematologic malignancy prescribed ibrutinib for ≥ 1 week at Yale New Haven Hospital from 2014 to 2019 to identify serious infections defined as those requiring inpatient management. We collected demographic, clinical and oncologic data. Chi-squared tests were used to determine factors associated with an increased risk of infection. Results A total of 254 patients received ibrutinib including 156 with CLL, 89 with NHL and 9 with other leukemias. Among these, 21 underwent HSCT, 9 complicated by GVHD. There were 51 (20%) patients with serious infections including 45 (17.7%) bacterial, 9 (3.5%) viral and 5 (2%) IFI (1 pulmonary cryptococcosis, 4 pulmonary aspergillosis). Anti-mold prophylaxis was prescribed to 7 (2.8%) patients, none of whom developed IFI. Risk factors associated with serious infection included ECOG score ≥ 2 (OR 4.6, p &lt; 0.001), concurrent steroid use (≥ 10 mg prednisone daily for ≥ 2 weeks; OR 3.0, p &lt; 0.001), neutropenia (OR 3.6, p &lt; 0.01), lymphopenia (OR 2.4, p &lt; 0.05) and maximum ibrutinib dose of 560 mg (OR 2, p &lt; 0.05). There was a dose dependent increase in infections based on number of chemotherapy regimens prior to ibrutinib initiation: 14.3% with 0, 19.7% with 1-2 and 28.7% with ≥ 3 prior treatments. Conclusion The incidence of serious infection in hematologic patients on ibrutinib was higher than previously reported (20% versus 11%) but the rate of IFI was lower (2% versus 4%). High ECOG score, leukopenia, steroids, and higher ibrutinib doses were associated with an increased risk for serious infection. Targeted antimicrobial prophylaxis should be considered for patients on ibrutinib with these risk factors. Improving functional status may also reduce the risk of infection in patients on ibrutinib. Disclosures All Authors: No reported disclosures

scholarly journals Invasive Fungal Infections after Anti-CD19 Chimeric Antigen Receptor-Modified T-Cell Therapy: State of the Evidence and Future Directions

2021 ◽  
Vol 7 (2) ◽  
pp. 156
Author(s):  
Will Garner ◽  
Palash Samanta ◽  
Ghady Haidar
Keyword(s):  
Risk Factors ◽  
T Cell ◽  
Cell Therapy ◽  
Chimeric Antigen Receptor ◽  
Fungal Infections ◽  
Antigen Receptor ◽  
Invasive Fungal Infections ◽  
T Cell Therapy ◽  
Car T Cell ◽  
Car T

Studies describing invasive fungal infections (IFIs) after chimeric antigen receptor-modified T-cell (CAR-T-cell) therapy are limited. Although post-CAR-T-cell IFIs appear to be uncommon, they are associated with significant morbidity and mortality. Specific risk factors for IFIs in CAR-T-cell recipients have not been fully characterized and are often extrapolated from variables contributing to IFIs in patients with other hematologic malignancies or those undergoing hematopoietic cell transplant. Optimal prophylaxis strategies, including the use of yeast versus mold-active azoles, also remain ill-defined. Further research should investigate key risk factors for IFIs and establish an evidence-based approach to antifungal prophylaxis in these patients in order to improve clinical outcomes.

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